Dupilumab Improves Severe Asthma Outcomes, Regardless of Baseline OCS Dose

Patients with severe asthma who depend on oral corticosteroids (OCS) may experience significant reductions in exacerbations and improvements in lung function when treated with the fully human monoclonal antibody dupilumab, regardless of the patient’s baseline OCS dosage. These findings were included in a poster presentation for the 2021 CHEST Annual Meeting, held virtually October 17 to 20.

The study was a post hoc analysis of the phase 3 VENTURE study (ClinicalTrials.gov Identifier: NCT02528214) which included patients with OCS-dependent severe asthma who were treated with either 300 mg dupilumab every 2 weeks or placebo. The post-hoc analysis evaluated outcomes in patients grouped by baseline optimized OCS dose, assessing the following endpoints: 1) the OCS dose; 2) the proportion of patients that no longer required OCS at week 24; 3) the adjusted annualized severe exacerbation rate; and 4) the least squares (LS) mean change from baseline in the pre- and post-bronchodilator forced expiratory volume in 1 second (FEV1) at week 24.

Among patients receiving an OCS dose of less than 10 mg/day at baseline, those in the dupilumab (n=46) and placebo (n=36) groups were receiving mean OCS doses of 6.1 mg/day and 6.2 mg/day, respectively. In contrast, those with a baseline OCS dose of 10 mg/day or more received mean OCS doses of 14.5 mg/day in the dupilumab arm (n=57) and 14.6 mg/day in the placebo group (n=71) at baseline.

Compared with placebo, treatment with dupilumab was associated with a reduction in the daily OCS dose from baseline to week 24 in the groups of patients that received OCS of less than 10 mg/day (LS mean difference, 2.1 mg; 95% CI, 0.8–3.3; P <.01) and in those receiving 10 mg/day or more (3.3 mg; 95% CI, 1.0–5.5; P <.01).

In the group of patients with a baseline OCS dose less than10 mg/day, a higher proportion of patients treated with dupilumab no longer needed OCS at week 24 (72% vs 42%; odds ratio [OR], 3.8; 95% CI, 1.4–10.0; P <.01). Similarly, a higher group of patients treated with dupilumab who had a baseline OCS dose of 10 mg/day or more did note require OCS at follow-up (37% vs 23%; OR, 2.3; 95% CI, 1.0–5.4; P <.05). The researchers note that not all of the patients with a baseline OCS dose 10 mg/day or more were eligible for down-titration to 0 mg/day per the study’s protocol.

Treatment with dupilumab was also associated with a 71% reduction in the annualized rate of severe asthma exacerbations in patients with a baseline OCS dose of less than 10 mg/day (P<.01) and a 48% reduction in the annualized rate of severe exacerbations in patients with a baseline OCS dose of 10 mg/day or more (P <.05).

At the 24-week follow-up, treatment with dupilumab vs placebo was also associated with improvements in pre-bronchodilator FEV1 in the group of patients with a baseline OCS dose 10 mg/day or more (LS mean difference, 0.26 L; 95% CI, 0.09–0.43; P <.01). In contrast, there were numerical improvements in pre-bronchodilator FEV1 in patients with a baseline OCS dose of less than10 mg/day (LS mean difference, 0.15 L; 95% CI, –0.04 to –0.33; P >.05).

Compared with placebo, treatment with dupilumab was also associated with significant improvements in post-bronchodilator FEV1 at follow-up in patients with baseline OCS doses of less than10 mg/day (LS mean difference, 0.20 L; 95% CI, 0.05–0.35; P <.05) and 10 mg/day or more (LS mean difference, 0.18 L; 95% CI, 0.02–0.34; P <.05).

Disclosure: Multiple authors declared affiliations with the pharmaceutical industry. Please refer to the original article for a full list of disclosures.

Reference

Domingo C, Jorge R, Mario M, et al. Dupilumab reduced oral corticosteroid use and improved clinical outcomes regardless of baseline OCS dose in patients with uncontrolled, severe asthma in the Liberty Asthma VENTURE study. Presented at: CHEST 2021; October 17-20, 2021; Orlando, FL/Virtual. Abstract A1893-A1897.